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トクトミ トモハル
Tomoharu Tokutomi
徳富 智明 所属 川崎医科大学 医学部 臨床医学 小児科学 職種 特任教授 |
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| 論文種別 | 症例報告 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Hypomethylation of a centromeric block of ICR1 is sufficient to cause Silver-Russell syndrome. |
| 掲載誌名 | 正式名：Journal of medical genetics ISSNコード：0022-2593/1468-6244 |
| 掲載区分 | 国外 |
| 出版社 | BMJ |
| 巻・号・頁 | 58(6),pp.422-425 |
| 著者・共著者 | Ken Higashimoto,Hijiri Watanabe,Yuka Tanoue,Hidefumi Tonoki,Tomoharu Tokutomi,Satoshi Hara,Hitomi Yatsuki,Hidenobu Soejima |
| 発行年月 | 2021/06 |
| 概要 | Silver-Russell syndrome (SRS) is a representative imprinting disorder. A major cause is the loss of methylation (LOM) of imprinting control region 1 (ICR1) within the <italic>IGF2/H19</italic> domain. ICR1 is a gametic differentially methylated region (DMR) consisting of two repeat blocks, with each block including three CTCF target sites (CTSs). ICR1-LOM on the paternal allele allows CTCF to bind to CTSs, resulting in <italic>IGF2</italic> repression on the paternal allele and biallelic expression of <italic>H19</italic>. We analysed 10 differentially methylated sites (DMSs) (ie, seven CTSs and three somatic DMRs within the <italic>IGF2/H19</italic> domain, including two <italic>IGF2</italic>-DMRs and the <italic>H19</italic>-promoter) in five SRS patients with ICR1-LOM. Four patients showed consistent hypomethylation at all DMSs; however, one exhibited a peculiar LOM pattern, showing LOM at the centromeric region of the <italic>IGF2</italic>/<italic>H19</italic> domain but normal methylation at the telomeric region. This raised important points: there may be a separate regulation of DNA methylation for the two repeat blocks within ICR1; there is independent control of somatic DMRs under each repeat block; sufficient <italic>IGF2</italic> repression to cause SRS phenotypes occurs by LOM only in the centromeric block; and the need for simultaneous methylation analysis of several DMSs in both blocks for a correct molecular diagnosis. |
| DOI | 10.1136/jmedgenet-2020-106907 |
| PMID | 32447322 |
| PermalinkURL | https://syndication.highwire.org/content/doi/10.1136/jmedgenet-2020-106907 |